Possible involvement of calcineurin in retinoic acid-induced inhibition of leukemic HL-60 cell proliferation.
Differentiation of leukemic HL-60 cells by all transretinoic acid (ATRA) resulted in a reduced rate of growth. Cyclosporin A and FK506, at concentrations that inhibited calcineurin activity, abrogated the ATRA-induced inhibition of HL-60 cell growth but these immunosuppressants had no effect on the ATRA-induced granulocytic differentiation. Treatment with 1 microM ATRA led to a progressive increase in calcineurin phosphatase activity of HL-60 cells; the increase in this activity appeared to parallel the functional change of HL-60 cells during granulocytic differentiation. Increase in calcineurin activity was concordant with the increased expressions of calcineurin A and calcineurin B subunit proteins. The FKBP12 expression increased during ATRA-induced differentiation and expression of cyclophilin A remained unchanged. We propose that the increased expression of calcineurin is involved in the ATRA-induced inhibition of HL-60 cell proliferation, as in the case with 1,25alpha-dihydroxy-vitamin D3.
Kihira
H
H
The Second Department of Internal Medicine, Mie University School of Medicine, Tsu, Mie 514, Japan.
Hiasa
A
A
Yamamoto
M
M
Katayama
N
N
Kuno
T
T
Ohtsuka
K
K
Shiku
H
H
Nishikawa
M
M
D019703:Calcineurin / Q000378:metabolism*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000096:biosynthesis; D002147:Calmodulin / Q000096:biosynthesis; D002352:Carrier Proteins / Q000096:biosynthesis; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects*; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D016572:Cyclosporine / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D006098:Granulocytes / Q000166:cytology / Q000187:drug effects; D018922:HL-60 Cells; D006360:Heat-Shock Proteins / Q000096:biosynthesis; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007700:Kinetics; D019696:Peptidylprolyl Isomerase / Q000096:biosynthesis; D011090:Polyenes / Q000494:pharmacology; D020123:Sirolimus; D016559:Tacrolimus / Q000494:pharmacology; D022021:Tacrolimus Binding Proteins; D014212:Tretinoin / Q000494:pharmacology*
D002147:Calmodulin; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D006360:Heat-Shock Proteins; D007166:Immunosuppressive Agents; D011090:Polyenes; D014212:Tretinoin; D016572:Cyclosporine; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019703:Calcineurin; D022021:Tacrolimus Binding Proteins; D019696:Peptidylprolyl Isomerase; D020123:Sirolimus; D016559:Tacrolimus